In fighting the body's immune system, HIV owes part of its success to its ability to destroy those cells normally recruited to mount the body's counter-attack against the HIV-infected cells. Lying at the crux of such success is a viral protein called Nef, which protects its infected host while simultaneously destroying the neighboring uninfected cells of the immune system, according to scientists at the Gladstone Institute of Virology and Immunology.
"It's HIV going both ways, playing offense and defense," said Warner C. Greene, MD, PhD, director of the Gladstone Institute of Virology and Immunology and UCSF professor in the departments of medicine and microbiology and immunology. "It is a rather remarkable example of the cunning strategy the AIDS virus employs to help ensure its survival and spread."
Researchers have long known that cells surrounding an HIV-infected cell are eliminated by way of a programmed self-destructive process known as apoptosis. And Nef, the researchers knew, somehow plays a key role in triggering this destruction. Now in a study published in the April 12, 2001 issue of Nature, Gladstone scientists have discovered that Nef also protects its infected host cell from the detrimental effects by using the same trigger. The new study shows that Nef does this by binding to and inhibiting a protein called ASK1, a key player in apoptosis.
"If we could effectively block the assembly of Nef and ASK1, it could lead to the premature death of the HIV-infected host cell," Greene said. "The HIV infection process would then be short-circuited and the virus might simply die out because it would not have sufficient time to fully reproduce itself."
Achieving such a block will require discovering and developing a molecule that interrupts the assembly of Nef and ASK1, helping to "tip the balance in favor of the body effectively dealing with the virus," he said.